The general metabolic, hormonal and cellular enzyme activity patterns will be defined, characterizing the marked hyperlipidemia developing on carbohydrate diets in the desert rodent Acomys cahirinus in whom low insulin secretion capacity has been established. A link will be sought between the low insulin availability, inadequate peripheral substrate assimilation (adipose tissue, muscle) and the prefential channeling of nutrients to the liver, leading to excessive induction of hepatic enzymes of glycolysis and lipogenesis with lipoprotein overproduction and retention in the circulation. The animals will be challenged with diets of varying carbohydrate, protein and fat content to find out whether the level of intake or the nature of the nutrient correlate with the hyperlipidemia and to what extent is a low insulin responder predisposed to obesity, glucose intolerance or ketosis on a fat-rich diet. The role of insulin and glucagon will be investigated in regulating the nutrient-induced metabolic changes. The results will be integrated and evaluated to better understand the nature of the diabetic diathesis and propensity to hyperlipidemia in the human low insulin responder facing the contemporary caloric affluence. The colony in Jerusalem, derived from direct domestication of Acomys cahirinus from its native habitat, will be expanded and developed to make these animals available to all investigators wishing to explore the pancreatic responses, metabolic adjustments and long-term complications occurring in a low insulin responder maintained on different diets. In later stages of this project, comparative metabolic studies will be undertaken on other rodents overlapping in the population area but varying in their feeding habits to explore whether the low insulin response in A. cahirinus represents a unique derangement or a typical adaptation to desert food of low caloric density.